Aspergillus spp. mycotoxins infect corn, cotton, sorghum and nuts. Controlling mycotoxin biosynthesis or fungal development would decrease its devastating health and economic impact. Because signaling pathways tend to be conserved in Aspergillus spp, the model system Aspergillus nidulans is used to study regulation of mycotoxin production and morphological development. Aspergillus spp. produce resistant structures: sclerotia in Aspergillus flavus and Aspergillus parasiticus and fruiting bodies called cleistothecia in A. nidulans. Because it is posited that sclerotia derive from cleistothecia that lost the capacity to produce spores, it is likely that conserved signaling pathways controlling cleistothecial development also control sclerotial formation in the major producers of the carcinogenic mycotoxin aflatoxin, A. flavus and A. parasiticus. Molecular studies over the control of cleistothecial or sclerotial development are limited. Only a few regulatory genes are known. We found that deletion of the veA gene completely blocks mycotoxin production as well as the formation of resistant structures in A. nidulans, A. flavus and A. parasiticus. We also found that morphological development and secondary metabolism is also controlled by this global regulator across genera. The VeA protein is a fungal-specific promising target for a control strategy;however, it does not present homology to previously described proteins. The main goal of this proposal is to further characterize the regulatory mechanism through which VeA controls mycotoxin biosynthesis and morphogenesis, particularly resistant structure development, in the model system, A. nidulans. In this study we propose to: 1. Characterize VeA interacting proteins, and 2. Generate and characterize suppressor mutants to identify the genetic elements downstream from veA involved in ST production. Because of the conserved nature of fungal regulatory networks across species and the fact that VeA has only been found in fungi, a control strategy involving VeA may be effective against mycotoxin contamination by Aspergillus spp. and against other plant and animal pathogens. PUBLIC HEALTH RELEVANCE: This AREA grant proposal involves the study of the mechanism of action of VeA, a fungal global regulator that controls the biosynthesis of secondary metabolites, such as potent carcinogenic mycotoxins, as well as development. In this study we propose to use the well known model filamentous fungus Aspergillus nidulans. VeA is conserved in different fungal species, particularly in Ascomycetes spp. The fact that VeA is unique to fungi and is conserved in different fungal species, makes veA a valuable possible target to control not only plant pathogens but human and animal pathogens. In this proposal we will examine 1. VeA interacting proteins involved in this regulatory system, and 2. Suppressor mutants to identify the genetic elements downstream from veA involved in mycotoxin production. These studies will provide valuable insight into this important fungal regulatory mechanism.